Supplementary Material for: Five-year sustained response to nivolumab in hepatocellular carcinoma following serious immune-related hepatitis

Introduction
Hepatocellular carcinoma (HCC) holds high cancer mortality worldwide. Immunotherapy-based combination therapy, currently the first-line (1L) standard of care in advanced HCC, has shifted the treatment paradigm concerning both efficacy and safety outcomes. Data on immune-related adverse events surrogacy for efficacy outcomes is mixed.

Case Report
We report the case of a 58-year-old male with chronic Hepatitis C virus infection who presented with a voluminous shoulder HCC metastasis. Albeit an initial significant biochemical response with 1L sorafenib, progressive disease after 3 months plus a bleeding complication led to treatment discontinuation. Second-line nivolumab, although yielding a rapid clinical and biochemical response, was permanently ceased after 12 weeks due to a grade 3 immune-related hepatitis. Notably, 5 years post-treatment, the patient sustains a major biochemical and radiographic response.

Discussion
This case highlights an unusual and sustained response to nivolumab treatment in HCC, following early treatment discontinuation due to severe hepatotoxicity.